Size and heterologous elements predict metastases in malignant phyllodes tumours of the breast

Koh, Valerie Cui Yun; Thike, Aye Aye; Nasir, Nur Diyana Md; Yip, George W.; Bay, Boon Huat; Tan, Puay Hoon

doi:10.1007/s00428-017-2257-1

Cited by 33 publications

(25 citation statements)

References 38 publications

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“…Koh et al recently reported a series of 83 cases of malignant PT showing that large tumours (≥90 mm) containing malignant heterologous elements disclosed significantly worse metastasis-free survival and a trend for poorer overall survival. 26 Multivariate analysis confirmed marked cytological atypia as an independent prognostic factor for cumulative incidence of phyllodes-related recurrence.…”

Section: Discussionmentioning

confidence: 82%

Prognostic factors in phyllodes tumours of the breast: retrospective study on 166 consecutive cases

et al. 2020

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BackgroundPhyllodes tumours (PTs) are rare fibroepithelial tumours accounting for <1% of all breast tumours. We assessed clinicopathological features and their prognostic effect in a single-institution patients’ cohort.MethodsPatients diagnosed with PT between 2001 and 2018 at our institution were identified. Clinical, surgical and pathological features were collected. Phyllodes-related relapse was defined as locoregional or distant recurrence (contralateral excluded), whichever first.ResultsA total of 166 patients were included: 115 with benign, 30 with borderline and 21 with malignant PTs. Features associated with malignant PT were younger age, larger T size, higher mitotic count, marked cytological atypia, stromal overgrowth, stromal hypercellularity, necrosis and heterologous differentiation (all p<0.01). The majority of patients with malignant PT underwent mastectomy (63.2% vs 3% of benign/borderline, p<0.001) and had negative surgical margins (83.3%). 4-year cumulative phyllodes-related relapse incidence was 7% for benign/borderline PT and 21.3% for malignant PT (p=0.107). In the entire cohort, marked cellular atypia and heterologous differentiation were associated with worse phyllodes-related relapse-free survival (HR 14.10, p=0.036 for marked vs mild atypia; HR 4.21, p=0.031 for heterologous differentiation present vs absent). For patients with benign PT, larger tumour size was associated with worse phyllodes-related relapse-free survival (HR 9.67, p=0.013 for T>5 cm vs T≤2 cm). Higher tumour-infiltrating lymphocytes (TILs) were associated with borderline and malignant PT (p=0.023); TILs were not associated with phyllodes-related relapse-free survival (HR 0.58, p=0.361 for TILs>2% vs≤2%). Overall, four patients died because of PT: three patients with malignant and one with borderline PT.ConclusionsPatients with malignant PT had increased rates of phyllodes-related relapse and phyllodes-related death. Cellular atypia and heterologous differentiation were poor prognostic factors in the entire cohort; large tumour size was associated with an increased risk of phyllodes-related relapse in benign PT.

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Section: Discussionmentioning

confidence: 82%

Prognostic factors in phyllodes tumours of the breast: retrospective study on 166 consecutive cases

et al. 2020

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“…In this case, she was diagnosed of distant metastasis to stomach after the symptoms of frequent melena and drop of hemoglobin level. However, she had anemia in the beginnings (hemoglobin level was in the range of 8 10 mg/dL) before total mastectomy. CT of chest- abdomen showed no overt evidence of distant metastasis while intraluminal lesions of gastrointestinal tract might be unclear in CT scan.…”

Section: Discussionmentioning

confidence: 99%

“…The median size of PTs is about 4 cm. Those size larger than 10 cm are less than 10% of PTs, and the largest one so far is up to 50 × 50 cm reported by Islam et al [ 4 , 5 ] Approximately 10–15% of PTs are malignant, and only 10–26% of malignant PTs are found with metastasis [ 6 – 8 ].…”

Section: Introductionmentioning

confidence: 99%

A giant malignant phyllodes tumor of breast post mastectomy with metastasis to stomach manifesting as anemia: a case report and review of literature

et al. 2020

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Background: Phyllodes tumors (PTs) are well known for local recurrence and progression. Less than 10% of these tumors grow larger than 10 cm. Distant metastases have been reported in up to 22% of malignant PTs, with most metastases being discovered in the lungs. PTs of the breast rarely metastasize to the gastrointestinal tract, and reported cases are scarce. To date, a review of the English literature revealed only 3 cases, including our case, of PTs metastasis to stomach. Case presentation: An 82-year-old female patient had 10-year-duration of palpable huge tumor on left breast which was in rapid growth in recent months. Total mastectomy of left breast was performed thereafter, and pathology diagnosis was malignant phyllodes tumor. Adjuvant radiotherapy was suggested while she declined out of personal reasons initially. For PTs recurred locally on left chest wall 2 months later, and excision of the recurrent PTs was performed. She, at length, completed adjuvant radiation therapy since then. Six months later, she was diagnosed of metastasis to stomach due to severe anemia with symptom of melena. Gastrostomy with tumor excision was performed for uncontrollable tumor bleeding. Conclusion: For PTs presenting as anemia without known etiologies, further studies are suggested to rule out possible gastrointestinal tract metastasis though such cases are extremely rare. Management of metastatic gastric tumor from PTs should be done on a case-to-case basis, surgical intervention may be needed if there is persistent active bleeding despite medical treatment. Adjuvant radiotherapy is recommended in borderline and malignant PTs with tumor-free margin < 1 cm and high-risk malignant tumors. Adjuvant chemotherapy or target therapy may be helpful for metastatic PTs. Molecular and genomic techniques may predict clinical outcomes of benign and borderline PTs more precisely.

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“…Benign PTs are reported to recur locally at a rate of 10–17%, while the recurrent likelihood is higher for borderline and malignant PTs, at 14–25% and 23–30%, respectively . Malignant PTs also have an increased potential to metastasise to distant sites such as the lungs, bone, brain, and liver, leading to a poor prognosis and a higher risk of death as there is limited success of radiotherapy and chemotherapy .…”

Section: Introductionmentioning

confidence: 99%

Genomic characterisation of breast fibroepithelial lesions in an international cohort

Nasir

Rajasegaran

et al. 2019

The Journal of Pathology

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Fibroepithelial lesions (FELs) are a heterogeneous group of tumours comprising fibroadenomas (FAs) and phyllodes tumours (PTs). Here we used a 16-gene panel that was previously discovered to be implicated in pathogenesis and progression, to characterise a large international cohort of FELs via targeted sequencing. The study comprised 303 (38%) FAs and 493 (62%) PTs which were contributed by the International Fibroepithelial Consortium. There were 659 (83%) Asian and 109 (14%) non-Asian FELs, while the ethnicity of the rest was unknown. Genetic aberrations were significantly associated with increasing grade of PTs, and were detected more in PTs than FAs for MED12, TERT promoter, RARA, FLNA, SETD2, TP53, RB1, EGFR, and IGF1R. Most borderline and malignant PTs possessed ≥ 2 mutations, while there were more cases of FAs with ≤ 1 mutation compared to PTs. FELs with MED12 mutations had significantly higher rates of TERT promoter, RARA, SETD2, EGFR, ERBB4, MAP3K1, and IGF1R aberrations. However, FELs with wild-type MED12 were more likely to express TP53 and PIK3CA mutations. There were no significant differences observed between the mutational profiles of recurrent FAs, FAs with a history of subsequent ipsilateral recurrence or contralateral occurrence, and FAs without a history of subsequent events. We identified recurrent mutations which were more frequent in PTs than FAs, with borderline and malignant PTs harbouring cancer driver gene and multiple mutations. This study affirms the role of a set of genes in FELs, including its potential utility in classification based on mutational profiles.Conflict of interest statement: PHT, BTT, and PT jointly hold patent applications for PCT/SG2015/050107 (Breast fibroadenoma susceptibility mutations and use thereof) and PCT/SG2015/050368 (Method and kit for pathologic grading of breast neoplasms). The other authors declare no competing interests.

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Size and heterologous elements predict metastases in malignant phyllodes tumours of the breast

Cited by 33 publications

References 38 publications

Prognostic factors in phyllodes tumours of the breast: retrospective study on 166 consecutive cases

Prognostic factors in phyllodes tumours of the breast: retrospective study on 166 consecutive cases

A giant malignant phyllodes tumor of breast post mastectomy with metastasis to stomach manifesting as anemia: a case report and review of literature

Genomic characterisation of breast fibroepithelial lesions in an international cohort

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